We are proposing to establish a Vermont Center on Tobacco Regulatory Science (VCTRS) at the University of Vermont (UVM) in collaboration with colleagues from Brown University, Johns Hopkins University, University of Minnesota, and University of Pittsburgh. The VCTRS will focus on researching the effects of new tobacco products in vulnerable populations, with special emphasis on reducing the addiction potential of cigarettes and other tobacco products by reducing their nicotine content and examining the impact of these products on biomarkers of exposure and health outcomes. Each of these foci was selected to address crosscutting and specific priorities of the FDA outlined in RFA-DA-13-003. We will establish an administrative core at UVM that will provide the senior scientific and administrative leadership and support that is essential to a vibrant and successful multidisciplinary center of research excellence. We are proposing three primary research projects that will be complemented by a program of developmental research. In addition to this research mission, the VCTRS will also establish a predoctoral and postdoctoral training program in tobacco regulatory science that will be primarily located at UVM but will also include training at Brown University and Johns Hopkins University. The research and training missions will be led by experts in addictions research in collaboration with accomplished experts in biomarkers and health outcomes from the disciplines of biochemistry, family practice, internal medicine, and obstetrics and gynecology. There is strong institutional support for establishing the VCTRS at UVM that runs from the departmental level through the highest administrative offices and extending out into key Vermont state offices that are involved in establishing and implementing the state's tobacco control policies (see Letters of Support). Below we expound on each of these key aspects of establishing the VCTRS. One other point that we want to mention now, and expound upon below, is our plan to study the potential of very low nicotine content (VLNC) cigarettes for reducing the abuse liability of cigarettes. This should not be confused with earlier failed efforts to develop light cigarettes for the same purpose. VLNC cigarettes actually have lower nicotine content as opposed to the earlier ineffective strategy of keeping nicotine content the same and attempting to lower nicotine yield through ventilation, which smokers often circumvented with compensatory smoking. These are different strategies and, while still limited, the evidence on VLNC cigarettes lowering the abuse liability of cigarettes is quite promising.